Single Dose of Modafinil Improved Memory in People in Remission from Depression

August 3, 2017 · Posted in Potential Treatments · Comment 

memory aidModafinil is a wake-promoting medication used to treat narcolepsy, but studies have also shown that it can improve cognition in people with schizophrenia or attention deficit hyperactivity disorder. It may also help people with lingering cognitive difficulties after recovering from a depression. A 2016 article in the journal Biological Psychiatry reported that a single 200mg dose of modafinil improved performance on tests of episodic memory and working memory (but not planning or attention).

The study by researcher Barbara Sahakian and colleagues included 60 patients who had recently recovered from a depression. They took some cognitive tests to establish a baseline of their performance. A week later, they were given either a placebo or a single dose of modafinil, and two hours later they completed the cognitive tests again. The modafinil group performed better on the memory-related tasks.

While side effects were limited, two participants who received modafinil had sleep disturbances that night.

Longer-term studies are needed to determine whether modafinil is safe and effective if taken over a longer period of time. Cognitive dysfunction can interfere with daily tasks such as work or school and put people at greater risk of relapse, so effective treatments have the potential to greatly improve quality of life for people in remission from depression.

Kynurenine Pathway Suggests How Inflammation is Linked to Schizophrenia

December 20, 2016 · Posted in Neurochemistry · Comment 


The kynurenine pathway describes the steps that turn the amino acid tryptophan (the ingredient in turkey that might make you sleepy) into nicotinamide adenine dinucleotide. This pathway might be a connection between the immune system and neurotransmitters involved in schizophrenia.

A recent autopsy study by researcher Thomas Weickert and colleagues explored this link by determining that in the brains of people with schizophrenia and high levels of inflammation, messenger RNA for Kynurenine Aminotransferase II (KATII, a step on the kynurenine pathway) was elevated in the dorsolateral prefrontal cortex compared to the brains of people who died healthy and those with schizophrenia but low levels of inflammation.

The KATII mRNA levels also correlated with mRNA levels of inflammatory markers such as glial fibrillary acidic protein and interleukin-6.

Blood measures related to the kynurenine pathway also differentiated people with schizophrenia from healthy controls. People with schizophrenia had lower levels of tryptophan, kynurenine, and kynurenic acid in their blood. The low levels of kynurenic acid in the blood were correlated with deficits in working memory and smaller volume of the dorsolateral prefrontal cortex.

Weickert and colleagues suggest that blood levels of kynurenic acid might provide a measurable indicator of the degree to which people with schizophrenia are experiencing problems with executive functioning (planning and decision-making) and loss of brain volume.

Transcranial Direct Current Stimulation May Improve Cognition in Schizophrenia

April 13, 2015 · Posted in Potential Treatments · Comment 

transcranial direct current stimulationA recent study by Robert Smith and colleagues studied the use of transcranial direct current stimulation (tDCS) in patients with schizophrenia. TDCS is very low level current that has a positive (anode) or negative (cathode) electrode. Anodal stimulation of the cortex is usually associated with positive effects on mood and cognition. Patients received either five sessions of active tDCS for 20 minutes (at 2 milli Amps) or a sham stimulation for the same period. Then, one day after the final session, the patients were measured on a variety of scales for cognition and illness. Patients who received the active tDCS showed more improvements in working memory and attention than patients who received the sham treatment.

There was no difference in the two groups’ schizophrenic symptoms, including hallucinations. Smith and colleagues suggest that the improvements in cognition may result from changes to brain connectivity networks, since abnormalities in these networks have been identified in patients with schizophrenia and bipolar disorder.

Replications of this type of study are needed to clarify the effect of tDCS on cognition in schizophrenia, but given the safety and convenience of the procedure, the findings are promising.

RTMS Improves Working Memory In Patients With Schizophrenia

May 22, 2013 · Posted in Potential Treatments · Comment 

rTMSRepetitive transcranial magnetic stimulation (rTMS) may improve working memory in patients with schizophrenia, according to a small study published by Zafiris J. Daskalakis and colleagues in Biological Psychiatry in 2013. Patients with schizophrenia received either 20 Hz rTMS over the left and right prefrontal cortex or a sham treatment, and the rTMS improved working memory on a particular task, the n-back task, wherein patients are asked to recall whether a stimulus they’re currently viewing is the same as the previous one they viewed, or one they viewed several times back. Twenty sessions of rTMS over a period of 4 weeks brought memory back to the levels seen in normal controls.

Editor’s Note: Since many patients with bipolar disorder also have deficits in prefrontal-based memory and performance even when euthymic, it will be important to see if rTMS would also be helpful in these patients.  RTMS at 20 Hz increases neuronal activity as measured by PET scan of the prefrontal cortex and other regions of the brain, and this lasts for at least 48 hours after each treatment.

Since many patients with schizophrenia and bipolar disorder show deficits in prefrontal activity at baseline, the normalization of these alterations could relate to the memory improvement.  This proposition could be tested relatively easily.